O00418 (EF2K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic elongation factor 2 kinase
Short name=eEF-2 kinase
Short name=eEF-2K
EC=2.7.11.20

Alternative name(s):
Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase

Gene names

Name:

EEF2K

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	725 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. Ref.1 Ref.8
Catalytic activity	ATP + [elongation factor 2] = ADP + [elongation factor 2] phosphate. Ref.1
Enzyme regulation	Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent By similarity.
Subunit structure	Monomer or homodimer Potential.
Domain	The catalytic domain is located to N-terminal region. The neighbor region contains the calmodulin-binding domain. Ref.4
Post-translational modification	Autophosphorylated. Phosphorylated by AMP-activated protein kinase AMPK at Ser-398 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-78 resulting in improved protein stability, higher EE2F phosphorylated and subsequently reduced rate of protein synthesis. Phosphorylation by other kinases such as CDK1 and MAPK13 at Ser-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease EEF2K activity and promote protein synthesis. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17
Sequence similarities	Belongs to the protein kinase superfamily. Alpha-type protein kinase family. Contains 1 alpha-type protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	insulin receptor signaling pathway Traceable author statement. Source: Reactome protein autophosphorylation Inferred from direct assay Ref.1. Source: UniProtKB translational elongation Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro calmodulin binding Inferred from direct assay Ref.1. Source: UniProtKB elongation factor-2 kinase activity Inferred from direct assay Ref.1. Source: UniProtKB translation factor activity, nucleic acid binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 725	725	Eukaryotic elongation factor 2 kinase		PRO_0000086936
Regions
	Domain	116 – 326	211	Alpha-type protein kinase
	Nucleotide binding	296 – 302	7	ATP By similarity
	Region	594 – 610	17	Calmodulin-binding Potential
	Region	610 – 627	18	Pseudosubstrate/autoinhibitory domain Potential
Amino acid modifications
	Modified residue	18	1	Phosphoserine Ref.7 Ref.9 Ref.10 Ref.13 Ref.14 Ref.15
	Modified residue	27	1	Phosphoserine Ref.9 Ref.14
	Modified residue	31	1	Phosphoserine Ref.9 Ref.14
	Modified residue	69	1	Phosphotyrosine Ref.9
	Modified residue	70	1	Phosphoserine Ref.9
	Modified residue	71	1	Phosphoserine By similarity
	Modified residue	78	1	Phosphoserine; by TRPM7 Ref.17
	Modified residue	135	1	Phosphoserine Ref.11
	Modified residue	348	1	Phosphothreonine Ref.13
	Modified residue	359	1	Phosphoserine; by MAPK13 and CDK1 Ref.5 Ref.12
	Modified residue	366	1	Phosphoserine; by RPS6KA1 and RPS6KB1 Ref.6
	Modified residue	398	1	Phosphoserine; by AMPK Ref.8
	Modified residue	445	1	Phosphoserine Ref.10
	Modified residue	470	1	Phosphoserine Ref.9 Ref.13 Ref.14 Ref.15
	Modified residue	474	1	Phosphoserine Ref.9 Ref.13 Ref.14
	Modified residue	477	1	Phosphoserine Ref.13
	Modified residue	500	1	Phosphoserine; by PKA By similarity
Natural variations
	Natural variant	23	1	H → R. Ref.3 Ref.18 Corresponds to variant rs9935059 [ dbSNP | Ensembl ].		VAR_033915
	Natural variant	75	1	P → A. Ref.18 Corresponds to variant rs17841292 [ dbSNP | Ensembl ].		VAR_033916
	Natural variant	291	1	T → M in a colorectal adenocarcinoma sample; somatic mutation. Ref.18		VAR_041534
	Natural variant	361	1	Q → R. Ref.1 Ref.3 Corresponds to variant rs4783453 [ dbSNP | Ensembl ].		VAR_058405
	Natural variant	433	1	R → W. Ref.18 Corresponds to variant rs56137739 [ dbSNP | Ensembl ].		VAR_041535
	Natural variant	609	1	D → H. Ref.18		VAR_041536
Experimental info
	Mutagenesis	366	1	S → A: Abrogates phosphorylation by RPS6KB1. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O00418 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: 9D2900E50EFF12DA	FASTA	725	82,144
	10 20 30 40 50 60 MADEDLIFRL EGVDGGQSPR AGHDGDSDGD SDDEEGYFIC PITDDPSSNQ NVNSKVNKYY 70 80 90 100 110 120 SNLTKSERYS SSGSPANSFH FKEAWKHAIQ KAKHMPDPWA EFHLEDIATE RATRHRYNAV 130 140 150 160 170 180 TGEWLDDEVL IKMASQPFGR GAMRECFRTK KLSNFLHAQQ WKGASNYVAK RYIEPVDRDV 190 200 210 220 230 240 YFEDVRLQME AKLWGEEYNR HKPPKQVDIM QMCIIELKDR PGKPLFHLEH YIEGKYIKYN 250 260 270 280 290 300 SNSGFVRDDN IRLTPQAFSH FTFERSGHQL IVVDIQGVGD LYTDPQIHTE TGTDFGDGNL 310 320 330 340 350 360 GVRGMALFFY SHACNRICES MGLAPFDLSP RERDAVNQNT KLLQSAKTIL RGTEEKCGSP 370 380 390 400 410 420 QVRTLSGSRP PLLRPLSENS GDENMSDVTF DSLPSSPSSA TPHSQKLDHL HWPVFSDLDN 430 440 450 460 470 480 MASRDHDHLD NHRESENSGD SGYPSEKRGE LDDPEPREHG HSYSNRKYES DEDSLGSSGR 490 500 510 520 530 540 VCVEKWNLLN SSRLHLPRAS AVALEVQRLN ALDLEKKIGK SILGKVHLAM VRYHEGGRFC 550 560 570 580 590 600 EKGEEWDQES AVFHLEHAAN LGELEAIVGL GLMYSQLPHH ILADVSLKET EENKTKGFDY 610 620 630 640 650 660 LLKAAEAGDR QSMILVARAF DSGQNLSPDR CQDWLEALHW YNTALEMTDC DEGGEYDGMQ 670 680 690 700 710 720 DEPRYMMLAR EAEMLFTGGY GLEKDPQRSG DLYTQAAEAA MEAMKGRLAN QYYQKAEEAW AQMEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase." Ryazanov A.G., Ward M.D., Mendola C.E., Pavur K.S., Dorovkov M.V., Wiedmann M., Erdjument-Bromage H., Tempst P., Parmer T.G., Prostko C.R., Germino F.J., Hait W.N. Proc. Natl. Acad. Sci. U.S.A. 94:4884-4889(1997) [PubMed: 9144159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, VARIANT ARG-361. Tissue: Glial tumor.
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-23 AND ARG-361. Tissue: Lymph.
[4]	"Mapping the functional domains of elongation factor-2 kinase." Pavur K.S., Petrov A.N., Ryazanov A.G. Biochemistry 39:12216-12224(2000) [PubMed: 11015200] [Abstract] Cited for: AUTOPHOSPHORYLATION, DOMAIN.
[5]	"A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta." Knebel A., Morrice N., Cohen P. EMBO J. 20:4360-4369(2001) [PubMed: 11500363] [Abstract] Cited for: PHOSPHORYLATION AT SER-359.
[6]	"Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase." Wang X., Li W., Williams M., Terada N., Alessi D.R., Proud C.G. EMBO J. 20:4370-4379(2001) [PubMed: 11500364] [Abstract] Cited for: PHOSPHORYLATION AT SER-366 BY RPS6KA1 AND RPS6KB1, MUTAGENESIS OF SER-366.
[7]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398." Browne G.J., Finn S.G., Proud C.G. J. Biol. Chem. 279:12220-12231(2004) [PubMed: 14709557] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-398.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-27; SER-31; TYR-69; SER-70; SER-470 AND SER-474, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-445, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner." Smith E.M., Proud C.G. EMBO J. 27:1005-1016(2008) [PubMed: 18337751] [Abstract] Cited for: PHOSPHORYLATION AT SER-359.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; THR-348; SER-470; SER-474 AND SER-477, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-27; SER-31; SER-470 AND SER-474, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-470, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"The channel-kinase TRPM7 regulates phosphorylation of the translational factor eEF2 via eEF2-k." Perraud A.L., Zhao X., Ryazanov A.G., Schmitz C. Cell. Signal. 23:586-593(2011) [PubMed: 21112387] [Abstract] Cited for: PHOSPHORYLATION AT SER-78.
[18]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-23; ALA-75; MET-291; TRP-433 AND HIS-609.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U93850 mRNA. Translation: AAB58270.1. AC009034 Genomic DNA. No translation available. BC032665 mRNA. Translation: AAH32665.1.
IPI	IPI00011689.
RefSeq	NP_037434.1. NM_013302.3.
UniGene	Hs.498892.
3D structure databases
ProteinModelPortal	O00418.
SMR	O00418. Positions 104-324, 527-645.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-207181.
STRING	O00418.
PTM databases
PhosphoSite	O00418.
Proteomic databases
PRIDE	O00418.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263026; ENSP00000263026; ENSG00000103319.
GeneID	29904.
KEGG	hsa:29904.
UCSC	uc002dki.1. human.
Organism-specific databases
CTD	29904.
GeneCards	GC16P022217.
H-InvDB	HIX0202251.
HGNC	HGNC:24615. EEF2K.
HPA	CAB007818.
MIM	606968. gene.
neXtProt	NX_O00418.
PharmGKB	PA134992891.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07338.
GeneTree	ENSGT00530000063613.
HOGENOM	HBG717344.
HOVERGEN	HBG002318.
InParanoid	O00418.
OMA	HKPPKQV.
OrthoDB	EOG43TZTX.
PhylomeDB	O00418.
Enzyme and pathway databases
BRENDA	2.7.11.20. 2681.
Pathway_Interaction_DB	p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	O00418.
Bgee	O00418.
CleanEx	HS_EEF2K.
Genevestigator	O00418.
GermOnline	ENSG00000103319. Homo sapiens.
Family and domain databases
InterPro	IPR017400. Elongation_factor_2_kinase. IPR011009. Kinase-like_dom. IPR004166. MHCK_EF2_kinase. IPR006597. Sel1-like. IPR011990. TPR-like_helical. [Graphical view]
Gene3D	G3DSA:1.25.40.10. TPR-like_helical. 1 hit.
KO	K08292.
Pfam	PF02816. Alpha_kinase. 1 hit. PF08238. Sel1. 4 hits. [Graphical view]
PIRSF	PIRSF038139. Elongation_factor_2_kinase. 1 hit.
SMART	SM00811. Alpha_kinase. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51158. ALPHA_KINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	52478.
SOURCE	Search...

Entry information

Entry name

EF2K_HUMAN

Accession

Primary (citable) accession number: O00418
Secondary accession number(s): Q8N588

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 28, 2009
Last modified:	January 25, 2012
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.